Sugar is something sweet to add to your food, but just like fat, different types of sugars play important roles in biology. Along with proteins, lipids (fats), and nucleic acids like DNA and RNA, glycans (sugars) are considered one of the building blocks of life. In our bodies, our cells are coated by a protective layer made of sugars, which helps protect them from pathogens. But it's also thought that about 80 percent of infectious viruses and bacteria can bind to some of these sugars. The spike protein of the coronavirus uses a sugar to efficiently bind to our cells, for example. The same team of scientists that made that discovery have now learned more about the receptors that sugars, and pathogens, can bind to.
"We have established how the sugars bind to and activate the so-called Siglec receptors that regulate immunity. These receptors play a major role, as they tell the immune system to decrease or increase activities. This is an important mechanism in connection with autoimmune diseases," said first study author Christian Büll Ph.D., a postdoctoral researcher at the Copenhagen Center for Glycomics (CCG) at the University of Copenhagen. The findings have been reported in the Proceedings of the National Academy of Sciences.
Siglec (sialic acid-binding immunoglobulin-like lectin) receptors are activated by carbohydrates called sialic acid sugars, which are often linked to glycoproteins and glycolipids. The interactions between sialic acid sugars and Siglec receptors are thought to play an important role in regulating the immune system. Dysfunctions in these interactions have been linked to human disease including autoimmune disorders, cancer, and infection.
This work elucidated some of the relationships between Siglecs and their binding partners.
"As part of the new study, we have created a cell library that can be used to study how various sugars bind to and interact with receptors. We have done this by creating tens of thousands of cells each containing a bit of the unique sugar language, which enables us to distinguish them from one another and to study their individual effect and process. This knowledge can help us develop better treatment options in the future," explained study co-author Associate Professor Yoshiki Narimatsu from CCG.
"The surface of the cells in the library is the same as the one found on cells in their natural environment. This means that we can study the sugars in an environment with the natural occurrence of e.g. proteins and other sugars, and we can thus study the cells in the form in which virus and bacteria find them," added Narimatsu.
The researchers also identified which sugars bind to a receptor that's involved in Alzheimer's disease.
"Our main finding concerns the Siglec-3 receptor. Mutations in the Siglec-3 receptor [are] already known to play a role in connection with Alzheimer's, but we did not know what the receptor specifically binds to. Our method has now identified a potential natural sugar that binds specifically to the Siglec-3 receptor. This knowledge represents an important step forwards in understanding the genetic defects that cause a person to develop the disease," said Christian Büll.